1. Field of the Invention
The present invention relates to a naphthalene diimide derivative, and, more particularly, to a naphthalene diimide-Zn(II) complex having selectivity for pyrophosphate, a method of preparing the complex and a method of detecting pyrophosphate using the complex.
2. Description of the Related Art
Recently, novel sensors for detecting essential substances and ions present in living organisms have been actively designed and researched. Supramolecular chemistry has greatly influenced the design of host compounds, which can be selectively coupled with ions or various kinds of guest compounds. Thus, fluorescent chemosensors, which make it easy to observe the selective coupling of the host compounds and the guest compounds using the change in fluorescence of fluorescent materials coupled with supramolecular compounds, have been developed.
The term “fluorescence” refers to a photochemical phenomenon occurring when photons having a predetermined wavelength (excitation wavelength) collide with indicator molecules, by which electrons are excited to a high energy level. Among various analysis methods, fluorescence analysis is very advantageous in that signals can be observed even at a concentration as low as 10−9 M due to the high sensitivity thereof.
Recently, research on fluorescent chemosensors for detecting cations, anions and neutral organic molecules using the photochemical phenomenon has been actively conducted.
Anions play an important role in wide-ranging chemical and biological processes. Therefore, fluorescent chemosensors based on anion-induced changes are considered very interesting because they have high upper detection limits and are easy to handle (Martinez-Manez R and Sancanon F, Chem. Rev. 2003, 103, 4419). In particular, phosphate ions and derivatives thereof play an important role in the transfer of signals and the storage of energy in the biological system. For example, pyrophosphate (PPi) is a product obtained by hydrolyzing ATP under cellular conditions, and is a biologically important target. The detection of pyrophosphate (PPi) has been conducted using a real-time DNA sequencing method (Ronaghi M et al., Anal. Biochem. 1996, 242, 84). Currently, the detection of pyrophosphate is also used for cancer research (Xu S et al., Anal. Biochem. 2001, 299, 188).
The detection and discrimination of pyrophosphate (PPi) based on changes in fluorescence has been a major goal of many research groups (Singh N J et al., Org. Lett. 2007, 9, 485; Kim S K et al., Tetrahedron 2006, 62, 6065; Gunnlaugsson T et al., Org. Biomol. Chem. 2005, 3, 48; Aldakov D and Anzenbacher P Jr., Chem. Comm. 2003, 1394; Gunnlaugsson T et al., Org. Lett. 2002, 4, 2449; Anzenbacher P et al., J. Am. Chem. Soc. 2000, 122, 9350 Nishizawa S et al., J. Am. Chem. Soc. 1999, 121, 9463; Lee H N et al., Org. Lett. 2007, 9, 243; Jang Y J et al., J. Org. Chem. 2005, 70, 9603; Cho H K et al., Chem Commun. 2005, 1690; Lee D H et al., Angew. Chem., Int. Ed. 2004, 43, 4777; Aldakov D and Anzenbacher P Jr., J. Am. Chem. Soc. 2004, 126, 4752; Mizukami S et al. J. Am. Chem. Soc. 2002, 124, 3920; Vance D H and Czarnik A W, J. Am. Chem. Soc. 1994, 116, 9397). In relation to this, the present inventors have reported that novel fluorescein derivatives exhibit prominent fluorescence amplification of red-shift when pyrophosphate (PPi) is added thereto at pH 7.4.
As described above, although various kinds of fluorescent chemosensors, which can selectively recognize pyrophosphate (PPi), have been disclosed, few fluorescent chemosensors that can recognize pyrophosphate (PPi) in aqueous solutions that are similar to the environment in living organisms have been disclosed (Jang Y J et al., J. Org. Chem. 2005, 70, 9603; Lee D H et al., Angew. Chem., Int. Ed. Engl. 2004, 43, 4777; Fabbrizzi L et al., Angew. Chem., Int. Ed. Engl. 2002, 41, 3811; Mizukami S et al., J. Am. Chem. Soc. 2002, 124, 3920), and only two kinds of fluorescent chemosensors based on the formation of excimers have been disclosed.
The term “excimer fluorescence” refers to a phenomenon in which, as the distance between fluorescent materials is decreased, energy is transferred therebetween, and thus a new kind of fluorescence is emitted at a longer wavelength than that of the maximum fluorescence value emitted from the original fluorescent material. Excimer fluorescence is advantageous in that, since fluorescence can be observed at a new maximum fluorescence value, fluorescence correction is not required, and thus changes in fluorescence are more positively discerned.
Teramae et al. have detected pyrophosphate (PPi) using a guanidium-pyrene system, but this guanidium-pyrene system was tested only in methanol, and, in this system, the selectivity for pyrophosphate (PPi) was only compared to that for inorganic phosphate (Pi) (Nishizawa S et al., J. Am. Chem. Soc. 1999, 121, 9463). Further, Hong et al. have reported a pyrene-Zn(II) complex as a PPi-selective fluorescent chemosensor, but this pyrene-Zn(II) complex was problematic in that it causes the formation of excimers corresponding to the reaction of ATP with PPi even if only a small amount (0.4 equivalents) of ATP is used (Lee D H et al., Angew. Chem., Int. Ed. 2004, 43, 4777).
As described above, to date, no fluorescent chemosensors having excellent selectivity for PPi compared to selectivity for ATP and Pi due to the formation of excimers in an aqueous solution have been reported.